Mercaptoethyl pyridines and method of preparing same



Patented Aug. 19, 1952 v 2,607,776 NT- OFFICE or PREPARING SAME jWilliam Howells Vinton, Wilmington, Del., asr r signor'; to E.' I..du.Pont de Nemours & Com- I Y gpany, Wilmington; DeL, a corporation of Delafid'bralvillig Application December 2771 I m; No. 637.481

I new; (omen-+290) I arms-amen1mm fto -n'ew substituted pyridine's andmore particularly to [beta-(a'cylthio) ethyllpyridines and theirhydrolysis products. "It alsorelates toprocessesionpreparing suchcompounds.

lBeta tacylthiol ethyl] pyridinesand their 1 hydrolyjsis productsconstitute a i hitherto unknown elasso'i'compounds. They'are ofconsiderable interest in chemical syntheses 1 because the acylthioderivative can be hydrolyzed to thecorrespon'dingiree thiol which canintum'be reacted with "various 'thiol-reactive materials. Moreov'erpthe'ireethiols are valuablein the com pounding-oi various typesof rubber.

' tan-object of this invention 'isjthe new class of organic compounds,viz. the [beta-(acylthio) ethyllpyridines *and their hydrolysisproducts. Another object 'is to provideprocesses' for the preparation ofthese cor npounds. Other ob- J'eets" will appear hereinafter.These-objects are accomplished by the in- "newer [beta-(acylthio)ethyllpyridines and their-hydrolysis products and the processes forpreparing them which are described below. These substitutedethylpyridines have thegeneral formulainwhich Y represents an acylradical or hydrogen. Theqprocessior-theiormation oi [beta-(acylthio)ethyl-l pyridines is illustrated by the following' equation tor thepreparation or '2-ibeta- .(acetylthioi ethyiipyridine:

onion. omen-an:

' 'o'moni'sgcm onion.

The vinylpyridinesused .in the preparation of [beta- (acylthio') ethyl]pyridines of this invention may be. prepared by dehydrating bet'apyridylethanols, e. g., by heating the .betaapyridylethanol' incontact:with an alkali metalhydroxidev at subat'mospheric pressure, "asdescribed in' U. S.

rilrcmionisn .omop mm application'Serial No. 605',835, filed 'July 18,1945',

now abandoned, by-L.-F. Salisbury. The invention is illustrated by'thefollowing examples in which the proportions of the 1n} gradients areexpressed as parts by weight.

Example I To 114 parts of thiolacetic acid cooled to 40 C. is addedrapidly with eflicient stirring 157.5 parts of '2-viny1p'yri'dine. Theincrease, in temperature of the reaction mixture, caused'by theexothermic reaction taking place, is checked by-means of strong externalcooling so that the reaction'tempe'rature gradually rises to 20 'C.where it is maintained until the reaction is complete. The progress ofthe reaction can'be followed by-iodine titration oi analcoholicsolu-,tion of 'a' small aliquot portion of thereaction mixture. Subsequentto-stirring the mixture at 20 C. for one hour after the addition of "thereactants such a titration shows that 96% of the thio'acetie acidhasreacted. Fractionation Analysis: I Calculated iorCgI-IuONS: C, 59.6%.}H, 6.08% N, 7.75% S,17.7%. Found: C, 60.62% H, 6.31%; N, 8.54%; S,16.97%.

Example II To a solution of 53 parts of dry'hydrogen chloride in 600parts of methanol is added slowly with cooling 106.2 parts of2-[,beta(acetylthio)- ethyllpyridine, whereupon 'a mild evolution ofheatoccurs .and the temperature reaches C. After standing at roomtemperature ior 16 hours, the acid. is neutralized-byaddition of asodium methylate solution prepared by dissolving 33.3 parts of sodium inmethanol, and the resulting precipitate 01' sodium chloride is filteredioff; After removal of the solvent from the filtrate, there is obtainedby fractionation under nitro -v gen 20 parts of2-(beta-mercaptoethyl)pyridine, a colorless liquid, boiling point 94 C.at 7 mm.

Analysis: Calculated for C'IHSNS: N, 10.08%; S, 23.00%; thiol S, 23.00%.Found: N, 10.91%; 8,2220%; 'thiol S, 230%. V,

- EmampZe IH .To 152 parts 01' thiolacetic acid cooled tov -40" C. isadded rapidly with eflicient stirring 26 ;6 parts of2-vinyl-fiethylpyridine. The increase in temperature of the reactionmixture, caused by the exothermic reaction taking place,

is controlled by strong external cooling softhat a temperature of C.is'not exceeded during the addition of the vinylpyridine. The reactionmixture is stirred at room temperature (about 25 C.) for anotherhour,"at which time iodine of Z-[beta-(acetylthio) tritratioln of analiquot portion of the reaction mixture shows that 98.4% of thethioacetic acid has reacted. Fractionation of the crude prode uct undernitrogen gives 10 parts (24% of th epijy), I ethyl] -5 ethylpyritiine,v; a faintly yellow liquid, boiling point"'l31 -136" C. at 9.5 mm.; 7 gs a j G. 25 1066x72 1.5377

SP 4C.

Analysis: Calculated for C11H15ONS2 c, 53.1%

H, 7.18%; N, 6.70%. Found C. '63.81%;{' I;j l V the use of a solvent;however, a non-reactive 7.44%; N (Dumas), 6.74%.

The invention of [beta-(acylthio)ethyHpyridines has been illustratedwith particular reference to 2: [beta- (acetylthio) -ethyllpyridine' and2- [betaacetylt-hio) ethyl] -5-ethylpyridine and their. preparation fromthiolacetic acid, and 2-.vinylpyridine and 2-vinyl-5-ethylpyridine,;.respectively. However,-other vinylpyridines having a vinyl group on anycarbon atom of the heterocyclic ring and optionally having hydrocarbonradicals attached to other carbon atoms in the heterocyclic ring, andother; carbothiolic acids maybe used to prepare the substitutedpyridines of this invention. Specific examples of such vinylpyridineswhich may be used includezB-vinylpyridine, 4-vinylpyridine,2-vinyl-5-methylpyri-, dine,- 2-propyl-4-vinylpyridine and 3-ethyl-4vinylpyridine. V In addition to thiolacetic acid, other saturatedaliphatic, or aromatic carbothiolic acids such as thiolnro ionic,thiolbutyric, hexahydrothiolbenzoic, thiolbenzoic; and 14-.butanedithiolic acids ''may be used., Thus, by reaction of theappropriate vinylpyridine and carbothiolic acid, the following specific[beta- (acylthio)ethvll-pyridines are formed: ti-[beta-(n-propionylthio) ethyllpyridine, {l-[beta-(hexahydrobenzoylthio)ethyllpyridine, ;2-. [beta- (benzoylthio) ethyl] 5 methylpyridine,2:propyl-4- [beta- (n-butyrylthio) ethyl] -pyridi ne, 3-ethyl-4- [beta-(acetylthio) ethyl] pyridine, and di [beta- (2 -pyridyll ethylldithiolsuccinate. The hydrolysis products of thesespecificacylthioethylpyrhdines are 3-(beta-mercaptoethyl)pyridine, 4-

(beta-mercaptoethyl)pyridine, 2-(beta-mercapmetrically equivalentproportions in the preparation of these acylthioethylp'yridinesL I Inthe process illustrated .by. Examples .1 and III the reaction;conditions employed are -not critical and lmay be variedoverwide'limits. Since thereaction between'the vinylpyridine and thecarbothiolic acid take'sfplace withevolution of heat, it is usuallypreferable tocool the reaction mixture during the addition of thevinyl-. pyridine to the pre-cooled carbothiolic, acid so as to, keep thereaction temperaturev within the. range of -50 C., and preferably belowC'., in order to prevent polymerization of the vinylpyridine. The useof'strong external cooling also makes it possible to addthevinylpyridinerapidly without losing appreciable quantities .of low boiling ;carbothiolic acids. If desired, the, reaction can be carried out withoutthe use of special cooling equipment by addingjthe vinylpyridine to thecarbothiolic, acid at a. ratewhichis slow enough that the reactiontemperature does not exceed about C. during the addition of thereactants. After the addition of the reactants is completed the stirringof the mixture is continued at ordinary. temperatures or,

perature,"e; g., 50 C. oi'higher,

""" time sufiicient to complete the reaction. The

actual time required depends on the particular reactantsand="-the-=particular reaction temperature employed. For example, with2-vinylpyri- ;--dipe and thiolaeetic; acid, 1 hour at 20-25 C. iswsufiicient. -*The;progress of thereaction is con- -'venie'ntly followedby iodine titration of alcoholic solutions of small 'portions of thereaction mixture forunrea cted carbothiolic acid.

The reaction: proceeds satisfactorily without organic solvent may beused as a diluent to assist in controlling the temperature of thereaction mixture.- In :such case. or aniczliquids; suc i as benzene;saturated aliphatic hydrocarbons,.:and alcohols may be used; Thehydrolysis products of, ['beta-(acylthio)'- ethyllpyridines have beenillustrated with particular reference to beta-1(mercaptqethylipyridineprepared under certain;reactionconditions; however, other [betar(@cylthio) ethyllpyridines and other hydrolysis conditionsmay beemployed. In addition to'methanol', whichis used-in EXE- ample II, otheraliphatiq alcohols; preferablylow boiling alcohols such.as-ethylgpropyL-and iso-; butyl alcohols may be usedy; Likewisazothen strong acidcatalysts such as sulfuric and p -tolu enesulfonic acids maybe,employed; in'steadpf hydrogen chloride. r a 1 v The term f substituentiretreattee-nae;

nuc ear.

' any other substituent on carbon of the pyridine nucleus ishydrocarbon. 7 We,

3. A Z-Ebeta-(acylthio)ethyllpyridine wherein any other substituent oncarbon of the nucleus is hydrocarbon.

4. A ,ibeta- (acylthio) ethyllpyridine .1 any other substituent oncarbon of the pyridinenucleus is hydrocarbonh 5. A[beta-mercaptoethyl]pyridine lwherein any other substituent on' carbonof the pyridine nucleus is hydrocarbon.

6. 2- [beta-mercaptoethyl] pyridine. 7. Process for the prepartionof2-[beta-(acetylthio)ethyll-pyridine which comprises bringing thiolaceticacid and Z-vinylpyridine in contactin the liquid state at atemperature'loffnotmore than 50 C.,and recovering the resulting 2-[beta.

(acetylthioi-ethyl]pyridine.

8. Process for the preparation of 2- [beta-( ylthio)ethyl] pyridinewhich comprises bringing thiolacetic acid and 2-vinylpyridinein contactat, 20-25 C. and recoyering ,the resulting 2 b eta- (acetylthio)ethyllpyridine;

9. Process for the preparation of a [beta (acylthio) ethyl] pyridinewhich comprises bringing a saturated carbothiolic acid in contact with avinylpyr'idine in the liquid state at a temperature of not more than 50,C. and recovering the resulting [beta (acylthio)'ethyllpyridine,

10. Process according ,tdclaim" 9 wherein the the pyridine nitrogemivinylpyridine is; apart from entirely'hydrocarbon.

11. Process according claim 9 the;

pyridine vinylpyridine contains only carbon, hydrogen and the onepyridine nitrogen.

12. Process according to claim 17 wherein the carbothiolic acid additionproduct is hydrolyzed by contacting the same with a solution of a strongacid catalyst in an aliphatic alcohol.

13. A pyridine compound containing sulfur wherein said sulfur isbivalent and is attached through a --CH2CH2- bridging radical to carbonof the pyridine nucleus. the remaining valence of said bivalent sulfurbeing bonded to a monovalent radical of the class consisting of hydrogenand acyl radicals and wherein any other substituent on carbon of thepyridine nucleus is hydrocarbon.

14. Process for the preparation of a, [betamercaptoethyllpyridine whichcomprises bringing a saturated carbothiolic acid in contact with avinylpyridine wherein any substituent on nuclear carbon of the pyridinenucleus, other than the vinyl substituent, is hydrocarbon in the liquidstate at a temperature of not more than 50 C., hydrolyzing the resultingbeta-(acylthio)ethy1- pyridine by contacting the same with a solution,in an aliphatic alcohol, of a strong acid catalyst, and recovering the[beta-mercaptoethyllpyridine.

15. 2- [beta-(acetylthio) ethyl] -5-ethylpyridine.

16. Process for the preparation of 2-[beta-(acetylthio)ethyll-5-ethylpyridine which comprises bringing thiolaceticacid and 2--vinyl-5- ethylpyridine in contact in the liquid state at atemperature of not more than 50 C. and recovering the resulting 2-[beta-(acetylthio) ethyl] -5- ethylpyridine.

17. Process for the preparation of a pyridine compound containing sulfurwherein said sulfur is bivalent and is attached through a 19. Processaccording to claim 18 wherein the carbothiolic acid addition product ishydrolyzed by contacting the same with a solution of a strong acidcatalyst in an alkanol of one to four carbons.

WILLIAM HOWELLS VINTON.

REFERENCES CITED The following references are of record in the file ofthis patent:

Chem. Zentralblatt, 1939, II, p. 3412.

4. A (BETA-(ACYLTHIO)ETHER)PYRIDINE WHEREIN ANY OTHER SUBSTITUENT ONCARBON OF THE PYRIDINE NUCLEUS IS HYDROCARBON. 15.2-(BETA-(ACETYLTHIO)ETHYL)-5-ETHYLPYRIDINE.